1. Field of the Invention
The present invention relates to 3-(1H-tetrazol-5-yl)-oxanilic acid and salts thereof which are hydrophilic or soluble in water, a method for preparing these compounds and the use of them as antiallergic agent for treating and preventing allergic diseases such as bronchial asthma, rhinitis and conjunctivitis.
2. Description of the Prior Art
It has been known that there are a lot of morbigenous antigens in the living environment, which possibly cause allergic reaction in human body, such as house dusts, pollen, molds, drugs (e.g., aspirin, penicillin) or the like. Among allergic reactions, bronchial asthma or the like are referred to as IgE dependent type allergy in which IgE is strongly involved. If an antigen comes into contact with the surface of the cell membrane of a mast cell, the antigen and IgE antibody cause an antigen-antibody reaction. As a result, degranulation phenomenon is caused and the resulting granule secretes various chemical transmitters such as histamine, SRS-A (slow reacting substance of anaphylaxis), ECF-A (eosinophil chemotactic factor of anaphylaxis), heparin or the like thereby various kinds of allergic reaction are caused. In other words, the allergic diseases are caused as a result of hypersecretion of mucous gland, contraction of smooth muscles or the like because of the foregoing antigen-antibody reaction.
Among the foregoing chemical transmitters, histamine, SRS-A and ECF-A are considered to be particularly important so far as the human body is concerned. Therefore, it is effective to suppress the secretion of these chemical transmitters to protect and treat patients suffering from such diseases.
Thus, there have been proposed a variety of pharmaceutical preparations containing active components having histamine and SRS-A release inhibitory effect. Among them, drugs effective to asthma or other allergic diseases such as esters of 3-(1H-tetrazol-5-yl)oxanilic acid, for instance, ethyl ester and butyl ester thereof (hereunder referred to as MTB) have been known. In this respect, reference is made to Japanese Patent Publication for Opposition Purpose No.59-1705 (antiallergic compound) and Japanese Patent Unexamined Publication Nos. 61-151116 and 61-225121 (agent for treating asthma).
These esters of 3-(1H-tetrazol-5-yl)oxanilic acid such as MTB presents an excellent histamine and SRS-A release inhibitory effect and, therefore, they may be used as antiallergic agents and/or drugs for treatment or prevention of asthma. However, it is quite difficult to prepare an aqueous pharmaceutical preparation of these esters for some purposes and in general they are used in the dosage form of orally administered solid preparations since these compounds are hydrophobic or less soluble in water (Japanese Journal of Pharmacology, 1982, Vol. 32, pp. 689-697).
Generally speaking, when these compounds are used as drugs for treatment or prevention of asthma, it is preferred to adminster, to patients, such a drug locally and in the minimum effective amount thereof for the purpose of preventing the occurrence of any possible side effects which are possibly caused due to systemic administration of a large amount of drugs.
Accordingly, it is very desirable to adminster these drugs as an inhalant which makes it possible to administer the drugs even to the deep portion of the bronchus in the form of the fine particles of the solution thereof. For this reason, the drugs for treatment or prevention of asthma should be hydrophilic or soluble in water.